What’s the News: One of biologists’ favorite fantasies is a doctor who can fit inside a cell. This tiny physician, likely a device built from DNA, would make diagnoses by sensing molecules floating around the body that are signatures of certain diseases and would then release the appropriate drug.
While that vision is still a long way off, scientists have taken a significant step in that direction with a system that detects problems at several levels of cells’ machinery.
What’s the Context:
- Disease are frequently the result of malfunctioning proteins, which zip around taking care of the daily business of the body. Proteins are made using our DNA as templates; as described by the Central Dogma of biology, first DNA is transcribed into an mRNA molecule, which is then translated by cellular machinery into the protein. One way to tell whether a protein is abnormal is by checking the mRNA molecule for errors.
- The researchers’ first “biocomputer,” which they developed seven years ago, did just that. It consisted of a strand of DNA and a DNA-snipping enzyme.
- The DNA was designed to bind to mRNAs of specific proteins known to be involved in certain cancers. Once bound, if the mRNA was abnormal, the enzyme snipped the DNA one way, while if it was normal, the enzyme snipped another way. (It’s this binary calculation and the chain of events that results from it that give the system the “biocomputer” moniker.)
- If the mRNA was abnormal, the snipping resulted in the production of a piece of DNA that bound to the mRNA and kept it from getting made into (malfunctioning) proteins. Though it only worked in a test tube, it was pretty nifty.
How the Heck:
- Fast-forward to the present, when the researchers have adapted that system so that it responds to not just mRNA, but to several other kinds of molecules that could be involved in diseases, including microRNA, which regulate mRNA; certain kinds of proteins; and small molecules, like ATP.
- Since the malfunctions that cause disease can involve any combination of these, this promises a much more reliable diagnosis than mRNA alone. It’s the equivalent of monitoring a whole flurry of vital signs—like blood pressure, heart beat, and blood oxygen level—instead of just heart beat.
The Future Holds:
- Though the system is still confined to a test tube, many labs are looking for a way to take such tiny doctors into cells: one candidate is boxes made of DNA origami that open only when disease markers are present.
- Despite such research, the system is a very long way from any practical use. It hasn’t been tested in animals, and its biodegradability and functionality once it’s actually deployed are still big question marks. In the meantime, though, it can be used for research, the scientists point out. When it’s added to a solution taken from a patient, for example, it can give information about which of these markers show up in a given disease.
Reference: Binyamin Gil, et al. “Detection of Multiple Disease Indicators by an Autonomous Biomolecular Computer.” Nano Letters DOI:10.1021/nl2015872
Image credit: a.drian / flickr